为药物输送量身定制聚二氧化:通过COSMO-RS预测API兼容性
Alžběta Zemánková1, Alex Mathers1, Fatima Hassouna2
1Department of Physical Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic.
International journal of pharmaceutics
|February 16, 2026
概括
真实溶剂的导体样选模型 (COSMO-RS) 准确地预测了纳普洛克森在多二氧化 (POx) 中的溶解度. 现实的聚合物模型改善了预测,有助于药物辅助剂的早期配方选.
科学领域:
- 计算化学和材料科学.
- 药物配方和辅助剂查.
背景情况:
- 准确预测药物在聚合物中的可溶性对于制药配方至关重要.
- 聚二氧化 (POx) 是一种有潜力作为药物辅助剂的聚合物.
- 真实溶剂的导体样选模型 (COSMO-RS) 是用于预测物理性质的计算工具.
研究的目的:
- 评估COSMO-RS在三种不同的多二氧化 (POx) 中对纳素 (NAP) 溶解度的预测能力.
- 评估POx侧链结构对纳普洛克森可溶性预测的影响.
- 为了比较COSMO-RS.内的不同聚合物模型表示的准确性.
主要方法:
- 对于NAP-POx系统的固体-液体平衡 (SLE) 数据是通过差分扫描热度计 (DSC) 和逐步溶解方法实验确定的.
- 使用两个模型进行了COSMO-RS模拟:一个CH3顶COSKF调整器和一个更现实的CH3 / OH终结的五合体.
- 用西格玛分析分析对极性和相互作用进行了定性评估.
主要成果:
- 基于胺的COSMO-RS计算提供了更准确的热力学描述,并正确预测了实验性兼容性排名:聚-2-乙烯-2-zoline) (PEtOx) >聚-2-n--2-zoline) (PBuOx) >聚-2--2-zoline) (PPhOx).
- 该模型准确地解释了PBuOx在富含NAP的混合物中的结晶性损失.
- 绝对平均偏差较低的 pentamer 模型 (4.311.9 wt%) 与三元模型 (8.319.5 wt%) 相比,表明准确度提高.
结论:
- 特别是在COSMO-RS中,特别是使用现实的聚合物模型,如聚合物,对于预测POx助剂中纳普洛克森溶解度是有效的.
- 该研究表明,COSMO-RS在早期配方开发过程中区分密切相关的POx辅助剂的实用性.
- 使用COSMO-RS的计算查可以指导药物配方的适当辅助剂的选择.
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